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Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients.

Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany. PEPperPRINT GmbH, Heidelberg, Germany. Division of Functional Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg, Germany. Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Department of Neuropathology, Institute of Pathology, Heidelberg, Germany. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. Research Group Molecular Genetics of Breast Cancer, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Oncotarget. 2015;(15):13579-90
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Abstract

Liquid biopsies come of age offering unexploited potential to monitor and react to tumor evolution. We developed a cost-effective assay to non-invasively determine the immune status of glioblastoma (GBM) patients. Employing newly developed printed peptide microarrays we assessed the B-cell response against tumor-associated antigens (TAAs) in 214 patients. Firstly, sera of long-term (36+ months, LTS, n=10) and short-term (6-10 months, STS, n=14) surviving patients were screened for prognostic antibodies against 1745 13-mer peptides covering known TAAs (TNC, EGFR, GLEA2, PHF3, FABP5, MAGEA3). Next, survival associations were investigated in two retrospective independent multicenter validation sets (n=61, n=129, all IDH1-wildtype). Reliability of measurements was tested using a second array technology (spotted arrays). LTS/STS screening analyses identified 106 differential antibody responses. Evaluating the Top30 peptides in validation set 1 revealed three prognostic peptides. Prediction of TNC peptide VCEDGFTGPDCAE was confirmed in a second set (p=0.043, HR=0.66 [0.44-0.99]) and was unrelated to TNC protein expression. Median signals of printed arrays correlated with pre-synthesized spotted microarrays (p<0.0002, R=0.33). Multiple survival analysis revealed independence of age, gender, KPI and MGMT status. We present a novel peptide microarray immune assay that identified increased anti-TNC VCEDGFTGPDCAE serum antibody titer as a promising non-invasive biomarker for prolonged survival.